This project plans to further investigate the genetics of human trophoblastic disease by studying morphology, genetic markers and clinical follow up. To understand the full spectrum of entities, cases of partial hydatidiform moles, complete hydatidiform moles and of choriocarcinoma will be analysed. Special attention will be paid to the understanding of malignant transformation of complete moles. Complete hydatidiform mole is a conceptus without an embryo displaying generalized swelling of all the placental villi and gross trophoblastic hyperplasia. It is associated with a high risk (5-10%) of choriocarcinoma. The complete moles have a 46,XX or rarely a 46,XY karyotype, exclusively of paternal origin, resulting from duplication of a haploid sperm and dispermy respectively. The partial moles are triploid, the extra haploid set deriving from either parent but mostly from the father. They are associated with an embryo-fetus and evince focal mild-moderate trophoblastic hyperplasia. There has been no authenticated case of malignant disease following a partial molar pregnancy reported in the literature. Choriocarcinomas have hypotetraploid karyotypes and chromosomes with extensive rearrangements. The parental origin of the chromosomes not very well worked out. In order to establish exact genetic origin of complete and partial moles, the following polymorphic markers will be analysed from the molar tissues and the parental peripheral bloods: 1. Karyotype and chromosomal marker analysis by Q, R and C banding techniques. 2. Electrophoretic variant determination of several enzymes by standard starch gel electrophoresis. 3. Several restriction fragment length polymorphisms including the probe for Yield subunit of hCG, a particular polymorphism of which is reported to be associated with high risk for choriocarcinoma. Attempt will be made to identify the DNA transforming sequence(s) of the cellular genes responsible for the malignant transformation of the trophoblast by means of DNA transfection assay using NIH 3T3 and other cells. Cells from a series of homozygous 46,XX complete moles and the paternal bloods will be frozen in bulk quantities to allow for a comparison of paternal and effectively haploid DNAs of homozygous moles in order to resolve the allelic status and assignment of individual bands to specific loci of complex DNA probes with multiple bands.